"The U.S. Food and Drug Administration today approved a new use of Gleevec (imatinib) to treat children newly diagnosed with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL).
ALL is the most common type of pediatric "...
- Clinician Information:
Erwinaze Side Effects Center
Medical Editor: Charles Patrick Davis, MD, PhD
Erwinaze (asparaginase Erwinia chrysanthemi) is indicated for the treatment of acute lymphoblastic leukemia (ALL) patients who have developed an allergy (hypersensitivity) to E. coli derived asparaginase and pegaspargase chemotherapy drugs used to treat ALL. Erwinaze is not available as a generic drug. Side effects associated with Erwinaze treatment include serious allergic reactions (anaphylaxis), inflammation of the pancreas (pancreatitis), high blood levels of liver enzymes (abnormal transaminases and bilirubin), blood clotting, bleeding (hemorrhage), nausea, vomiting and high blood sugar (hyperglycemia).
Erwinaze is available in vials in the strength of 10,000 IUs (International Units) per ml when reconstituted. The recommended dose is in the strength of 25,000 IUs per injection. Erwinaze is injected directly into the muscle three times a week and works by breaking down one of the body's protein building blocks (the amino acid, asparagine) that is present in the blood, and is necessary for the growth of all cells. Leukemia cells cannot produce this protein building block. Severe side effects include hemorrhagic pancreatitis, anaphylaxis and irreversible glucose intolerance. There are no adequate and well-controlled studies of Erwinaze in pregnant women. It is not known whether Erwinaze can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Erwinaze should be given to a pregnant woman only if clearly needed. It is not known whether Erwinaze is secreted in human milk. Because many drugs are secreted in human milk, and because of the potential for serious adverse reactions in nursing infants from Erwinaze, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric patients (aged 2 -18) have been studied; before using this drug in a child, consultation with a pediatric specialist is suggested.
Our Erwinaze Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
What is Prescribing information?
The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.
Erwinaze FDA Prescribing Information: Side Effects
The following serious adverse reactions are discussed in greater detail in other sections of the label:
- Hypersensitivity reactions[see WARNINGS AND PRECAUTIONS]
- Pancreatitis [see WARNINGS AND PRECAUTIONS]
- Glucose intolerance [see WARNINGS AND PRECAUTIONS]
- Thrombosis and hemorrhage [see WARNINGS AND PRECAUTIONS]
The most common adverse reactions (incidence 1% or greater) with ERWINAZE treatment are systemic hypersensitivity, hyperglycemia, abnormal transaminases, fever, pancreatitis, local reactions, vomiting, nausea, thrombosis, hyperbilirubinemia, abdominal pain/discomfort, and diarrhea.
Because clinical trials are conducted under controlled, but widely varying conditions, adverse reaction rates observed in clinical trials of ERWINAZE cannot be directly compared to rates in the clinical trials of other drugs and may not reflect the rates observed in practice.
The data presented below are based on information collected from Study 1, a single-arm, multi-center, open-label, safety and clinical pharmacology trial and the ERWINAZE Master Treatment Protocol (EMTP), an expanded access program. Study 1 enrolled 58 patients treated on National Cancer Institute (NCI)-sponsored cooperative group ALL protocols who were unable to continue to receive pegaspargase due to hypersensitivity reactions. Patients received 6 doses of ERWINAZE 25,000 International Units/m² intramuscularly on a Monday, Wednesday, and Friday schedule as a replacement for each scheduled dose of pegaspargase remaining on their original treatment protocol. The Study 1 population included patients with a median age of 11 years (2 to 18 years); 59% were male, 78% were White, 10% were Black/African American, 5% were Asian, and 7% were other or unknown. A total of 35% were Hispanic or Latino. In Study 1, the number of ERWINAZE courses ranged from 1 to 9. In this study, 76% (44 of 58) completed all planned therapy. Fourteen (24%) patients stopped therapy prior to completion; seven due to allergic reactions, five due to physician or patient choice, one due to disease progression, and one due to discontinuation during frontline protocol. All other chemotherapy was continued according to the patient's prescribed treatment regimen [see Clinical Studies].
The EMTP trial had enrolled 1368 patients with ALL or lymphoblastic lymphoma who received ERWINAZE after developing systemic hypersensitivity to an E. coli-derived asparaginase. Of these 1368 patients, safety data were received for 940 patients with a median age of 9 years (1 to 76 years), 63% were male, 91% with leukemia, and 3% with lymphoma, and 6% with unknown disease information. Patients received ERWINAZE according to several schedules, and treatment center specifications with doses that ranged from 20,000 to 25,000 International Units/m² . In the EMTP trial, the planned number of doses of ERWINAZE ranged from 3 to 48 doses. Seventy-eight percent of patients (693 of 893) were able to receive all planned doses to complete their prescribed treatment regimen.
In Study 1, safety information included all reported adverse events with systematic collection of the following adverse events of special interest: allergy, pancreatitis, coagulopathy (hemorrhage, thrombosis or infarct), hyperbilirubinemia, hyperglycemia, hyperlipidemia, ketoacidosis, and CNS events (hemorrhage, thrombosis or infarction, cerebral venous thrombosis). EMTP safety data were derived from case report forms that collected adverse event information. The forms specifically requested information on occurrence of allergic reactions, thrombotic events, hemorrhagic events, hepatobiliary disorders, pancreatic disorders, and hyperglycemia.
The combined incidence of non-hematologic, non-infectious, adverse reactions (all Grades) occurring with ERWINAZE in Study 1 and the EMTP trial is provided in Table 1. The incidence of Grade 3 or greater non-hematologic, non-infectious adverse reactions occurring with ERWINAZE in each individual Study is provided in Table 2.
Table 1: Per Patient Combined Incidence of
Non-Hematologic and Non-Infectious Adverse Events N=998 (Study 1 + EMTP)
|Type of Event||Specific Response||Total Patients
(N / % of total)
|Allergic Reactions||Total||163 (16%)|
|Systemic hypersensitivity||136 (14%)|
|Local Reactions||31 (3%)|
|Anaphylaxis||8 ( < 1%)|
|Liver Abnormalities||Total||45 (5%)|
|Abnormal Transaminases||40 (4%)|
|Gastrointestinal Symptoms Not Associated with Pancreatitis||Total||42 (4%)|
|Abdominal Pain/Discomfort||14 (1%)|
|Clinical Coagulation Abnormalities||Total||28 (3%)|
|Hemorrhagic||9 ( < 1%)|
|Hyperammonemia||Hyperammonemia||7 ( < 1%)|
|Headache||Headache||8 ( < 1%)|
|Seizure||Seizure||7 ( < 1%)|
Table 2: Per Patient Incidence of Non-Hematologic,
Non-Infectious, Grade 3 and 4 Adverse Reactions
|Description of Event||Study 1
|Allergic Reactions||5 (9%)||42 (4%)|
|-Systemic Hypersensitivity||5 (9%)||34 (4%)|
|-Anaphylaxis||0||8 ( < 1%)|
|Hyperglycemia||1 (2%)||33 (4%)|
|Clinical Coagulation Abnormalities||0||9 ( < 1%)|
|-Thrombosis||0||8 ( < 1%)|
|-Hemorrhage||0||1 ( < 1%)|
|Pancreatitis||0||8 ( < 1%)|
|Liver Abnormalities||3 (5%)||7 ( < 1%)|
|-Abnormal Transaminases||3 (5%)||6 ( < 1%)|
|Hyperbilirubinemia||0||1 ( < 1%)|
|Gastrointestinal Symptoms Not Associated with Pancreatitis||1 (2%)||6 ( < 1%)|
|-Abdominal Pain/Discomfort||1 (2%)||3 ( < 1%)|
|-Nausea||1 (2%)||3 ( < 1%)|
|-Vomiting||1 (2%)||3 ( < 1%)|
|Fever||0||4 ( < 1%)|
|Diarrhea||0||3 ( < 1%)|
|Headache||0||2 ( < 1%)|
|Seizure||0||2 ( < 1%)|
There is a potential for immunogenicity with therapeutic proteins such as ERWINAZE. Immunogenicity assay results are highly dependent on several factors including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to ERWINAZE with the incidence of antibodies to other products may be misleading.
There is insufficient information to characterize the incidence of antibodies to ERWINAZE.
Read the entire FDA prescribing information for Erwinaze (Asparaginase Erwinia Chrysanthemi) »
Additional Erwinaze Information
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